Diffusion Kurtosis Imaging: A Possible MRI Biomarker for AD Diagnosis?

The purpose of this explorative study was to investigate whether diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) parameter changes are reliable measures of white matter integrity changes in Alzheimer's disease (AD) patients using a whole brain voxel-based analysis (VBA). Therefore, age- and gender-matched patients with mild cognitive impairment (MCI) due to AD (n = 18), dementia due to AD (n = 19), and age-matched cognitively healthy controls (n = 14) were prospectively included. The magnetic resonance imaging protocol included routine structural brain imaging and DKI. Datasets were transformed to a population-specific atlas space. Groups were compared using VBA. Differences in diffusion and mean kurtosis measures between MCI and AD patients and controls were shown, and were mainly found in the splenium of the corpus callosum and the corona radiata. Hence, DTI and DKI parameter changes are suggestive of white matter changes in AD.

Diagnostic value of MIBG cardiac scintigraphy for differential dementia diagnosis.

OBJECTIVE: Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy has shown the potential to discriminate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, these studies did not reflect clinical practice, as patients with ischemic heart disease, heart failure, diabetes mellitus, arterial hypertension, and hyperlipidemia and patients treated with antidepressants like trazodone were excluded. METHODS: This study aimed to evaluate the use of MIBG cardiac scintigraphy to diagnose DLB in clinical practice. Moreover, the potential diagnostic value of MIBG cardiac scintigraphy in patients with clinically ambiguous dementia diagnosis (DLB versus AD) was tested. Eighty-five patients with a possible clinical diagnosis of DLB entered the study. MIBG uptake was determined by calculating the heart-to-mediastinum-uptake ratio (H/M). RESULTS: The average H/M ratio was 1.42 ± 0.35. The number of core features for DLB and the H/M ratio were negatively correlated (p = 0.001; r = -0.360). With an H/M ratio cutoff of 1.68 in 20 patients with clinically ambiguous dementia diagnoses (DLB versus AD) at the moment of MIBG cardiac scintigraphy, 95% (19/20) of the patients were correctly classified as compared with clinical or definite diagnosis at follow-up, with sensitivity and specificity values for diagnosing DLB of 100% (16/16) and 75% (3/4), respectively. The H/M ratio was influenced only by age (p = 0.046; r = -0.217) and gender (p = 0.024) and not by any other variable studied. CONCLUSIONS: The MIBG cardiac scintigraphy H/M ratio is a possible diagnostic biomarker for DLB in routine clinical practice and might have an added diagnostic value in case of doubt between DLB and AD.

Increased CSF α-synuclein levels in Alzheimer's disease: correlation with tau levels.

BACKGROUND: Given the difficult clinical differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), growing interest resulted in research on α-synuclein as a potential cerebrospinal fluid biomarker (CSF) for synucleinopathies. METHODS: CSF α-synuclein-140 concentrations were determined by a prototype xMAP™ bead-based assay (Innogenetics NV, Belgium). In addition, CSF amyloid ß1-42 (Aß1-42), total tau (T-tau), and phosphorylated tau (P-tau181P) levels were determined. RESULTS: CSF α-synuclein levels were higher in AD patients as compared with cognitively healthy controls (P=.019) and patients with synucleinopathies (P<.001). CSF α-synuclein levels were correlated with T-tau (P<.001) and P-tau181P (P<.001) levels in autopsy-confirmed AD patients. A diagnostic algorithm using α-synuclein and P-tau181P discriminated neuropathologically confirmed AD from DLB patients, resulting in sensitivity and specificity values of 85% and 81%, respectively. CONCLUSION: Because CSF α-synuclein levels were significantly higher in AD as compared with synucleinopathies, α-synuclein might have a value as a biomarker for differential dementia diagnosis.

Cerebrospinal fluid Aß1-40 improves differential dementia diagnosis in patients with intermediate P-tau181P levels.

It is assumed that the concentration of amyloid-ß1-40 (Aß1-40) in cerebrospinal fluid (CSF) reflects the total amount of Aß protein in the brain and thus allows a better interpretation of inter-individual differences in Aß quantity than the Aß1-42 concentration. In this study, Aß1-40 was added to the existing CSF biomarker panel of Aß1-42, total tau (T-tau), and phosphorylated tau (P-tau181P) in order to test whether the accuracy of the differential dementia diagnosis improved. The concentration of Aß1-40 (INNOTEST® ß-amyloid(1-40) prototype version, Innogenetics NV, Belgium) and the other biomarkers (INNOTEST®) was determined in CSF samples from 80 Alzheimer's disease (AD) patients, 75 non-AD dementia patients, and 30 controls. A large proportion of the study population had autopsy-confirmed neurodegeneration (AD: 73/80 = 91%; non-AD: 38/75 = 51%). The levels of Aß1-40 were decreased in AD (10856 ± 4745 pg/mL) and non-AD patients (10519 ± 4491 pg/mL) when compared to controls (14760 ± 7846 pg/mL) (p = 0.002 and p = 0.001). The Aß1-42/Aß1-40 ratio was significantly decreased in AD (0.043 ± 0.021) as compared to non-AD patients (0.064 ± 0.027; p < 0.001) and controls (0.053 ± 0.023; p < 0.001). In order to differentiate AD from non-AD patients, a decision tree was constructed. The diagnostic accuracy of the decision tree that contained Aß1-42, Aß1-40, P-tau181P, and the Aß1-42/Aß1-40 ratio was significantly better than the diagnostic accuracy (80% versus 74%) of the decision tree without Aß1-40 and the Aß1-42/Aß1-40 ratio (p < 0.001). In conclusion, no difference in Aß1-40 CSF levels was found between AD and non-AD patients, but adding CSF Aß1-40 and the CSF Aß1-42/Aß1-40 ratio to a biomarker-based decision tree, might have an added value for discriminating AD from non-AD patients in case of intermediate CSF P-tau181P values.

Amyloid pathology influences aß1-42 cerebrospinal fluid levels in dementia with lewy bodies.

A significant proportion of patients with dementia with Lewy bodies (DLB) show Alzheimer's disease (AD) pathology like senile plaques and neurofibrillary tangles. Biomarkers in cerebrospinal fluid (CSF), such as amyloid-ß1-42 (Aß1-42), total tau (T-tau), and hyperphosphorylated tau (P-tau181P), are linked to the different pathological hallmarks of AD. We set up a study to investigate the influence of AD co-pathology on CSF biomarker concentrations and profiles in autopsy-confirmed DLB. DLB patients with senile plaques showed significantly lower CSF Aß1-42 concentrations than DLB patients without senile plaques, but not compared to the AD patients. There were no significant differences in CSF T-tau or P-tau181P concentrations between DLB patients with and without neurofibrillary tangles. A correlation was found between the number of APOE ε4 alleles and Aß1-42 CSF levels in DLB patients with senile plaques. Although the CSF biomarkers Aß1-42, T-tau, and P-tau181P have an added diagnostic value for the differential dementia diagnosis, concomitant amyloid pathology in DLB limits the use of CSF Aß1-42 for the differential diagnosis of AD versus DLB.